Integrated nasal nerve detector ablation-apparatus, nasal nerve locator, and methods of use

ABSTRACT

Systems and related methods for identifying and/or ablating targeted nerves are provided. A probe with stimulating electrodes and/or ablation members are provided. The probe may be inserted into a nasal cavity and current may be introduced through the electrodes to stimulate a targeted area. The response to stimulation may be used to identify the targeted nerve. Once identified, the ablation member may ablate the targeted nerve.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/575,889, filed Jan. 14, 2022, which is a continuation of U.S. patentapplication Ser. No. 15/786,306, filed Oct. 17, 2017, which claims thepriority to U.S. Provisional Application No. 62/408,920 filed on Oct.17, 2016, the contents of each of which are incorporated by referenceherein in their entirety for all purposes.

BACKGROUND

The major symptoms of allergic or non-allergic chronic rhinitis aresneezing, rhinorrhea, and night time coughing which are brought about bymucosal swelling, hyper-responsiveness of the sensory nerves, and anincreased number and augmented responses of secretory cells in theinferior turbinates, respectively. In particular, chronic severe nasalobstruction resulting from remodeling of submucosal tissues of theinferior turbinates due to dilation of the venous sinuses or fibrosiscan interfere with the quality of life.

One strategy is the surgical treatment of chronic rhinitis; that is tophysically eliminate the tissue of the inferior turbinate. Removal orablation of the mucosal tissue including the surface epithelial layerhas the disadvantage of postoperative complications such as crusting andan increased infection rate. Cauterization of the surface epithelia ofthe inferior turbinate using electrocautery, cryosurgery, or laseryields only short-term benefits to nasal breathing. Submucosal diathermyor cryosurgery also shows only a short-term effect. Turbinectomy isthought to have the greatest effect on nasal obstruction, and slightimprovement in some rhinitis patients but it is accompanied by severeadverse effects such as bleeding, crusting, and nasal dryness.

Golding-Wood, who recommended cutting the parasympathetic nerve fibersin the vidian canal to decrease the parasympathetic tone to the nasalmucosa, introduced a different approach for the treatment ofhypersecretion in 1961. Various approaches to the vidian canal weresubsequently developed, and the method was widely employed in the 1970s.However, the original technique was abandoned at the beginning of the1980s because of its irreversible complications such as dry eyes.

The pterygoid canal carries both parasympathetic and sympathetic fibers,namely the vidian nerve, to the sphenopalatine ganglion. Subsequently,these autonomic fibers, which relay in the sphenopalatine ganglion,reach the nasal mucosa through the sphenopalatine foramen as theposterior nasal nerves. The posterior nasal nerve, which follows thesphenopalatine artery and vein, arises within the sphenopalatineforamen. Similar to vidian neurectomy, selective interruption of theposterior nasal nerves, which interrupts the somatic afferentinnervation to the nasal mucosa, can be expected to reduce thehypersensitivity and axon reflexes of the nasal mucosa, however it hasno complications, like those of vidian neurectomy, since thesecretomotor supply to the lacrimal gland and the somatosensory supplyto the palate are intact, and overpenetration of the pterygoid canaldoes not occur.

Posterior nasal neurectomy, initially developed by Kikawada in 1998 andlater modified by Kawamura and Kubo, is a novel alternative method inwhich neural bundles are selectively cut or cauterized from thesphenopalatine foramen. Autonomic and sensory nerve fibers that passthrough the foramen anatomically branch into the inferior turbinate andare distributed around the mucosal layer. Therefore, selectiveneurectomy at this point enables physicians to theoretically avoidsurgical complications such as inhibition of lacrimal secretion.

There are three nerve bundles innervating the superior, middle andinferior turbinates. The posterior, superior lateral nasal branches offof the maxillary nerve (v2) innervate the middle and superiorturbinates. A branch of the greater palatine nerve innervates theinferior turbinate. Ablating these nerves leads to a decrease in orinterruption of parasympathetic nerve signals that contribute torhinorrhea in patients with allergic or vasomotor rhinitis.

Ablation (such as but not limited to cryoablation) allows for theablation of the posterior nasal nerves through overlying mucosa in anon-invasive procedure. However, there is no current method ofidentifying the location of the nasal nerves during the ablationprocedure other than through identifying anatomic landmarks. As aresult, these nerves may not be optimally targeted. One obstaclehindering this identification is the fact that these nerve fibers are2-3 millimeters beneath the mucosal surface. Possible strategies toidentify the nerve include taking advantage of the optical, sonic, andvisual properties of nervous tissue, identifying the sphenopalatineartery with which the posterior nasal nerves fibers travel, ordeveloping a method to identify the sphenopalatine ganglion, as it iscovered with a distinctive bony lamina and is in the general vicinity ofthe posterior nasal nerves. The present invention takes advantage ofthese differences to identify the posterior nasal nerves.

Electrical stimulation of parasympathetic nasal nerves causes anincreased frequency-dependent rate of flow of nasal secretions andarterial blood flow, as described by Änggård in his experiments withcats. In these experiments, Änggård delivered monophasic, square wavepulses with an intensity of 8 V and a duration of 1 msec to the distalend of the vidian nerve to 12 anesthetized cats, tracking vasodilationby measuring changes in gross pulse rate and tracking nasal secretionthrough collection in a well, ultimately finding that varyingstimulation frequencies affected the nature of the nasal secretion.Between 0.5 and 1.0 imp/sec, the stimulation resulted in a slight waterysecretion. Anywhere above 2.5 imp/sec resulted in a rich secretion thatsometimes overflowed in the nasal cavity. The disappearance rate of thenasal secretions and blood content also underwent an increase in rate asfrequency increased, suggesting that the electrical stimulation of theparasympathetic nerves simultaneously activated both the vascular andsecretory responses. However, when the cats were given atropine, anautonomic nerve system blocker, only the secretory response was blockedand the vascular response remained unaffected. This phenomenon showsthat while the postganglionic parasympathetic mediator of nasalsecretion is cholinergic, the mechanism that causes the vascularresponse in the nose is different and resistant to atropine andindomethacin.

The methods of this specific study improve upon the methods of pastexperiments (Tschalussow, 1913; Blier, 1930; Malcomson, 1959; Malm,1973, Drettner, 1963) studying the vasodilatory response of nasal mucosabecause the technique involving the ¹³¹I-labelled serum albumin avoidsthe previous source of error of nasal secretion affecting varyingmeasurements of the changes in the lumen of nasal passages and thechronic sympathetic denervation that had been performed on the catsisolated the parasympathetic nervous responses by preventing activationof sympathetic vasomotor fibers present in the vidian nerve. U.S. Pat.No. 6,526,318 to Ansarinia and related PCT Publication WO 01/97905 toAnsarinia, which are incorporated herein by reference, describe a methodfor the suppression or prevention of various medical conditions,including pain, movement disorders, autonomic disorders, andneuropsychiatric disorders. The method includes positioning an electrodeon or proximate to at least one of the patient's SPG, sphenopalatinenerves, or vidian nerves, and activating the electrode to apply anelectrical signal to such nerve. In a further embodiment for treatingthe same conditions, the electrode used is activated to dispense amedication solution or analgesic to such nerve.

U.S. Pat. No. 6,405,079 to Ansarinia, which is incorporated herein byreference, describes a method for the suppression or prevention ofvarious medical conditions, including pain, movement disorders,autonomic disorders, and neuropsychiatric disorders. The method includespositioning an electrode adjacent to or around a sinus, the duraadjacent a sinus, or falx cerebri, and activating the electrode to applyan electrical signal to the site. In a further embodiment for treatingthe same conditions, the electrode dispenses a medication solution oranalgesic to the site.

U.S. Pat. No. 6,788,975 to Whitehurst et al., which is incorporatedherein by reference, describes an implantable stimulator with at leasttwo electrodes that is small enough to have the electrodes locatedadjacent to a nerve structure at least partially responsible forepileptic seizures. The nerve structure may include a trigeminalganglion or ganglia, a trigeminal nerve, or a branch of a trigeminalnerve, a greater occipital nerve, lesser occipital nerve, thirdoccipital nerve, facial nerve, glossopharyngeal nerve, or a branch ofany of these neural structures. Electrical stimulation of such targetsmay provide significant therapeutic benefit in the management ofepilepsy.

BRIEF SUMMARY

Some embodiments of the present invention relate to methods and devicesfor identifying and/or ablating targeted nerves. While the presentinvention can be useful for a wide variety of nerves and conditionsassociated therewith, some embodiments of the invention are particularlyuseful for identifying and ablating nasal nerves to treat rhinitis asdescribed in more detail below. In many embodiments a probe withstimulating electrodes and a cryogenic ablation member are provided. Theprobe may be inserted into a nasal cavity and current may be introducedthrough the electrodes to stimulate a targeted area. Since a targetednerve such as a posterior nasal nerve may respond to such stimulationwith increased nasal secretion or blood flow, the response tostimulation may be used to identify the targeted nerve. Once identified,the cryogenic ablation member may ablate the targeted nerve to treatrhinitis.

Thus, in one aspect, a method is provided for identifying and ablating atargeted nasal nerve to induce secretory or vascular changes in nasaltissue innervated by the targeted nerve. The method includes inserting aprobe into a nasal cavity, the probe having a probe shaft with at leastone stimulating electrode and an ablation member disposed at a distalend of the probe shaft. The method further includes positioning thedistal end of the probe shaft so that the at least one stimulatingelectrode is placed in contact with a nasal tissue region, andintroducing an electrical current through the electrode via anelectrical source probe so as to stimulate at least one nasal nerveunderlying the nasal tissue region in contact with the at least onestimulating electrode. The method further includes identifying at leastone target nasal nerve and ablating the at least one identified targetnasal nerve with the ablation member to induce secretory or vascularchanges in tissue innervated by the at least one target nasal nerve.

In many embodiments of the method the target nasal nerve may beidentified by observing or measuring a response to the stimulationapplied. For example, the target nasal nerve may be identified byobserving a physiologic response to the electrical current. Thephysiologic response may an increased nasal secretion and/or anincreased arterial blood flow within the nasal cavity. The target nasalnerve may be identified by measuring at least one of a resistance, atemperature, and/or a degree of tumescence in the nasal cavity. Forexample, if a certain change in resistance or temperature is measured inresponse to the stimulation applied, the target nasal nerve may beidentified thereby. In some embodiments, a visual, audio or hapticfeedback may be provided indicating identification of the target nasalnerve.

In many embodiments of the method, the ablation member includes anexpandable structure which can aid in positioning the electrodes or theablation member. The pair of electrodes may be disposed on a surface ofthe expandable structure and positioning the probe includes expandingthe expandable structure so that the stimulating electrodes are placedin contact with the desired region of nasal tissue. As another example,positioning the probe includes expanding the expandable structure todisplace overlying mucosal tissue from a desired tissue region. In someembodiments of the method, ablating the identified targeted nasal nerveincludes expanding the expandable structure so that the ablation memberis in contact with the nasal tissue region overlying the identifiedtarget nasal nerve.

In many embodiments of the method, particular regions and/or nerves maybe desired to be targeted. In some embodiments, the targeted nasal nerveis a parasympathetic nerve that responds to electrical stimulation withincreased secretion or blood flow. For example, the targeted nasal nervemay be a posterior nasal nerve. The nasal tissue region targeted mayinclude a region of a nasal mucosa covering a medial pterygoid plate ofa sphenoid bone.

In many embodiments of the method, the electrical current may beoptimally controlled so that a desired response is obtained.Characteristics of the electrical current such as the voltage,frequency, pulse rate, and current may be controlled as desired. Forexample, introducing an electrical current through the electrodes mayinclude delivering electric pulses through the electrodes at a frequencyof 0.5 to 12 impulses per second.

In many embodiments of the method, the number and arrangement of theelectrodes may be selected to accurately target particular areas. Insome embodiments, a pair of electrodes may be used. The pair ofelectrodes may have a predetermined spacing so as to stimulate a certaindepth below a surface in contact with the electrodes. For example, theelectrodes may have a predetermined spacing so as to stimulate 1-5 mmunder the surface in contact with the stimulating electrodes. As anotherexample, the electrodes may have a predetermined spacing so as tostimulate 1-3 mm under the surface in contact with the stimulatingelectrodes. The electrodes may also be disposed on a distal tip that isreleasably coupled to the probe shaft.

In many embodiments the method further includes confirming that thetargeted nasal nerve has been ablated to ensure adequate response. Forexample, the method may include re-introducing an electrical currentthrough the electrode after ablating the at least one identified targetnasal nerve to confirm that target nasal nerve has been ablated.

In another aspect a method is provided for identifying a targeted nasalnerve associated with at least one symptom of rhinitis. The method mayinclude inserting a stimulator probe into a nasal cavity, the probehaving a probe shaft with a pair of electrodes disposed at a distal endof the probe shaft, positioning the distal end of the probe shaft sothat the stimulating electrodes are adjacent to a nasal mucosa region,and introducing an electrical current through the electrodes via anelectrical source coupled to the pair of electrodes such at least onenasal nerve underlying a nasal mucosa region in contact with thestimulating electrodes is stimulated. The method may further includemeasuring a response to the electrical current using the stimulatingelectrodes, repositioning the probe and stimulating the electrodes untila desired response is measured using the stimulating electrodes, andidentifying the location of at least one target nasal nerve when thedesired response is measured using the stimulating electrodes.

In many embodiments of the method, measuring the response includesmeasuring a parameter indicative of a change in at least one of nasalsecretion and/or arterial blood flow. In some embodiments of the method,the parameter indicative of a change in at least one of nasal secretionand/or arterial blood flow includes at least one of electricalresistance and/or temperature. For example, measuring the response mayinclude measuring a change in electrical resistance with the stimulatingelectrodes, the change in electrical resistance being indicative of achange in nasal secretion. The desired response may include a thresholdchange in electrical resistance measured after stimulating a targetedregion with the electrodes.

In many embodiments particular types of nerves and desired regions maybe targeted. For example, the targeted nasal nerve may be aparasympathetic nerve, and the tissue underlying the surface in contactwith the stimulating electrodes is stimulated in the presence of ananesthetic that does not impact parasympathetic nerves. As anotherexample, the desired region of the nasal mucosa may include a region ofthe nasal mucosa covering a medial pterygoid plate of a sphenoid bone.

In many embodiments of the method, the identified target nerve may beablated. In some embodiments, the method further includes applyingenergy to a region adjacent to the targeted nasal nerve to ablate thetargeted nasal nerve. For example, the identified target nerve may becryogenically ablated. In many embodiments, the method further includes,after applying energy to the region adjacent to the targeted nasalnerve, stimulating the region adjacent to the targeted nasal nerve withthe electrodes to confirm that the targeted nasal nerve has beenablated.

In many embodiments of the method, multiple locations of the targetednasal nerve may be mapped so that a separate probe may be used to ablateeach of the multiple locations. For example, the location of thetargeted nasal nerve includes a first location of the targeted nasalnerve and the method further includes storing coordinates of the firstlocation of the targeted nasal nerve, repositioning the probe andstimulating the electrodes until a desired response is measured at asecond location of the targeted nasal nerve using the stimulatingelectrodes, and storing coordinates of the second location of thetargeted nasal nerve. In some embodiments of the method, the methodfurther includes positioning a cryoablation member disposed at a distalend of a second probe at the coordinates of the first location andcryogenically ablating the first location of the targeted nasal nerve,and positioning the cryoablation member of the second probe at thecoordinates of the second location and cryogenically ablating the secondlocation of the targeted nasal nerve. As an example, the storedcoordinates of the first location and the second location and a currentposition of the cryoablation member are output on a display to guidepositioning of the cryoablation member at the first and secondlocations.

In another aspect, a stimulator probe is provided for identifying andablating at least one target nasal associated with at least one symptomof rhinitis. The probe may include a probe shaft having a proximal endand a distal end, at least two electrodes disposed at the distal end ofthe probe shaft, the at least two electrodes electrically coupled to anelectrical source, wherein the electrodes are configured to electricallystimulate at least one nasal nerve underlying a nasal surface in contactwith the electrodes in response to an electrical current generated bythe electrical source, at least one sensor disposed on the probe, thesensor configured to detect a parameter indicative of a change in atleast one of nasal secretion and/or arterial blood flow in response tothe electrical current, and a processor operatively coupled to theelectrical source and the sensor. The processor may be configured tocontrol the electrical current generated by the electrical source,receive the parameter indicative of a change in at least one of nasalsecretion and/or arterial blood flow from the sensor, and identify theat least one target nasal nerve based on the parameter indicative of achange in at least one of nasal secretion and/or arterial blood flow.The probe may further include an expandable ablation member configuredto ablate the at least one identified target nasal nerve to reduce atleast one symptom associated with rhinitis.

In many embodiments of the device, the electrodes may be designed and/orlocated to approach particular regions. For example, the electrodes maybe disposed on the expandable ablation member. As a further example, theexpandable ablation member may include an electrically non-conductivesurface, and the at least two electrodes may be disposed on theelectrically non-conductive surface of the ablation member. Theexpandable ablation member may be configured to inflate so as toposition the at least two electrodes adjacent to a desired tissueregion. In some embodiments of the device, the electrodes may be spacedapart in a range from 1 mm to 10 mm. For example, the electrodes may bespaced apart a sufficient distance to stimulate tissue 1-3 mm under thesurface in contact with the electrodes.

In many embodiments of the device, the at least two electrodes aredisposed on a distal tip that is releasably coupled to the probe shaft.The distal tip may include a connector that snaps to a connectionportion of the probe shaft that is proximal of the expandable ablationmember. The distal tip may extend from the connection portion to adistal end disposed distally of the expandable ablation member, and theat least two electrodes may be disposed at the distal end of the distaltip. In some embodiments, the distal tip may be made of polyamide ortempered stainless steel.

In many embodiments of the device, the probe shaft is sized so that thedistal end of the probe shaft can reach a nasal mucosa covering a medialpterygoid plate of sphenoid bone through a passage of a middle nasalmeatus from outside a nasal cavity.

In many embodiments of the device, the processor may control theelectrical current. In some embodiments of the device, the processor maybe configured to control at least one of a voltage, frequency, and/orpulse rate of the electrical current.

In many embodiments of the device, the sensor may detect certainparameters. The sensor may be configured to detect at least one ofelectrical resistance, temperature, and/or tumescence. For example, thesensor may be configured to detect a change in electrical resistance inan electrical signal passing through the electrodes after stimulation ofthe tissue, the change in resistance being indicative of a change innasal secretion after stimulation of the tissue.

In another aspect, a system and method for adjusting neural stimulationof a target, such as a nerve, is provided. In many embodiments, themethod includes electrically connecting at least one electrode to afirst tissue, applying a stimulus to the at least one electrode,observing a response of a second tissue, identifying an electrodeposition on the first tissue wherein a desired response occurs on thesecond tissue when the stimulus is applied to the at least oneelectrode, and fixing the at least one electrode in place at theidentified electrode position. In certain embodiments, the stimulusapplicator is disposable. The stimulus can be a voltage signal, acurrent signal, and can be preprogrammed. In certain embodiments, thevoltage or current signal is a controlled voltage or a controlledcurrent signal. In other embodiments, an estimated minimum stimulus iscalculated, and in yet another embodiment a stimulus profile isgenerated. The stimulated tissue may nerve tissue or mucosal tissue.Examples of a desired stimulus response include a change in airwaypatency, at least partial blockage of a neural impulse, and theinitiation of at least one neural impulse. A response can be directly orindirectly observed, either visually or with instrumentation.

In another aspect, a neural stimulation system is provided. The systemmay include at least one electrode electrically connected to a firsttissue, means for applying a stimulus to the at least one electrode,means for observing a response of a second tissue, means for identifyingan electrode position on the first tissue wherein a desired responseoccurs on the second tissue when the stimulus is applied to the at leastone electrode, and means for fixing the at least one electrode in placeat the identified electrode position.

In still another aspect, a computer program product may include acomputer readable medium having stored thereon computer executableinstructions that, when executed on a computer, causes the computer toperform a method of neural stimulation, including the steps of applyinga stimulus to at least one electrode electrically connected to a firsttissue, observing a response of a second tissue, and identifying anelectrode position on the first tissue, wherein a desired responseoccurs on the second tissue when the stimulus is applied to the at leastone electrode.

In another aspect, a neural stimulation system is provided. The systemmay include at least one electrode electrically connected to a firsttissue, a gross adjustment stimulator coupled to and delivering astimulus to the at least one electrode, a stimulus measurement subsystemin communication with the gross adjustment stimulator and having atleast one sensor, the at least one sensor measuring a response of asecond tissue, and a programming subsystem in communication with thestimulus measurement subsystem, the programming subsystem collectingdata from the group consisting of stimulus data and tissue responsedata.

In many embodiments, the systems and methods can be used to identifyautonomic nerves through a layer of overlying tissue (1-10 mm), with aspecific application in localizing the posterior nasal nervestransmucosally in the nasal cavity. In some embodiments, the apparatusmay include an expandable structure made of an electricallynon-conductive material attached to a cannula long enough to reach thenasal mucosa that covers the medial pterygoid plate of the sphenoid bonethrough the passage of the middle nasal meatus from the exterior of thebody.

In many embodiments, the expandable structure may be a balloon. On theouter surface of the balloon, there may be at least two electrodes thatare connected to a source of electricity which can be direct oralternating current. For example, the current may pass between the twoelectrodes through the underlying tissue. The electrodes may be arrangedin a mono-polar or bipolar arrangement. In some embodiments, more thantwo electrodes may be used. For example, the more electrodes that are onthe surface of the balloon, the more precisely the location of thenerves may be identified. However, there is also an upper limit of thenumber of electrodes on the balloon, because electrodes that are closetogether may not send electrical signals as deep into the mucosa. Inaddition, the pair of electrodes may be disposed on the exterior of thecannula in the general vicinity of where a nasal turbinate would be.

In many embodiments, the electrodes may be made of any conductivematerial, such as silver or zinc. In many embodiments, the electrodesmay be any shape, such as a circle or square, and may be adhered totheir respective surfaces by means such as adhesive, printing, thermalfusion, silver pen, or copper tape.

In many embodiments, the electrodes may be attached by their respectivewires that run parallel to the cannula and connect to a processor thatis located outside of the nasal cavity. In many embodiments, theprocessor may deliver electric pulses through the electrodes by way ofthe underlying tissue. In some embodiments, the processor may have thecapacity to alter the voltage, frequency, pulse rate, and current of theelectrical signal, as there are optimal ranges for nerve stimulation. Inaddition, the stimulator may use varying percentages of duty cycles forthe most effective stimulation of the nasal nerves. The minimum pulseduration for effective nerve stimulation is at least 0.03 microseconds,and all autonomic fibers have a probable low discharge rate of around1-2 imp/sec (Folkow, 1955). Research has suggested that thefrequency-dependent increase in nasal secretion and increased arterialblood flow for parasympathetic nasal nerves is observed whenstimulations are within the range of 0.5-12 impulses per second, withthe minimal effective frequency between 2-5 imp/sec and a maximumsecretion at 15 imp/sec (Anggird). The minimal effective frequency forthe aforementioned responses is between 2 and 5 hertz, with a maximum of10 to 15 hertz (Eccles and Wilson). Transcutaneous electrical nervestimulation (TENS) is also a common practice, suggesting that electricalstimulation of the nasal nerves is feasible over the mucosa. Althoughthere is no published research concerning the response time betweenelectrical stimulation and nasal secretion, the reaction is visiblynoticeable. Presumably, the closer the electrode is to the targetednasal nerve, the more the nasal secretions would be visible.

In many embodiments, the processor may electrically stimulate specificregions of the nasal cavity, which are defined by activating differentpairs of electrodes on the surface of the balloon. When the region thatis closest to the targeted nerve is activated, the change in nasalsecretion and arterial blood flow may be at their greatest. The twoelectrodes attached to the exterior of the cannula are designed to trackthis change in nasal secretion through measuring resistance,temperature, degree of tumescence or other parameters. Mucus contains avariety of electrolytes that are capable of conducting electricity, soas nasal secretion increases, in many embodiments, the two electrodes onthe cannula that are in contact with a nasal turbinate can track andrecord the decrease of resistance in the electrical signal. When theresistance is at the lowest, the pair of electrodes that were justactivated are in the nearest vicinity of the targeted nerves.

The foregoing presents a simplified summary of some embodiments of theinvention in order to provide a basic understanding of the invention.This summary is not an extensive overview of the invention. It is notintended to identify key/critical elements of the invention or todelineate the scope of the invention. Its sole purpose is to presentsome embodiments of the invention in a simplified form as a prelude tothe more detailed description that is presented later.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a device 100, in accordance with many embodiments.

FIG. 2 shows a sagittal view of a human head with the device and theendoscope in the nasal cavity, in accordance with many embodiments.

FIG. 3 shows a system 300, in accordance with many embodiments.

FIG. 4 shows connector 108 of device 100, in accordance with manyembodiments.

FIG. 5 shows distal end of device 100, in accordance with manyembodiments.

FIG. 6 shows an end effector 606 in accordance with many embodiments.

FIG. 7 shows an alternate end effector 706 in accordance with manyembodiments.

FIG. 8 shows a system 800 with a reusable stimulator tip 818 inaccordance with many embodiments.

FIGS. 9A-9C show views of reusable stimulator tip 818 and end effector806 in accordance with many embodiments.

FIG. 10 shows reusable stimulator tip 818 in accordance with manyembodiments.

FIG. 11 shows a coronal view of the relative location of an end effectorwith respect to anatomical landmarks in the nasal cavity, in accordancewith many embodiments.

FIG. 12A shows a diagram tracing the current flow through the tissuethat stimulates the nerve, in accordance with many embodiments.

FIG. 12B shows the diagram of FIG. 12A with an expandable member in aninflated position, in accordance with many embodiments.

FIG. 13 shows a system with conductivity sensors in accordance with manyembodiments.

FIG. 14 shows an image guided navigation system for ablation inaccordance with many embodiments.

FIG. 15 shows a flowchart describing a method of nerve localization, inaccordance with many embodiments.

FIG. 16 shows experimental data illustrating the relationship betweenpulse rate and stimulation frequency and secretion and stimulationfrequency.

FIG. 17 shows electrical stimulation parameters.

DETAILED DESCRIPTION

In the following description, various embodiments of the presentinvention will be described. For purposes of explanation, specificconfigurations and details are set forth in order to provide a thoroughunderstanding of the embodiments. However, it will also be apparent toone skilled in the art that the present invention may be practicedwithout the specific details. Furthermore, well-known features may beomitted or simplified in order not to obscure the embodiment beingdescribed.

FIG. 1 shows a device 100, in accordance with many embodiments. As canbe seen in FIG. 1 , device 100 may include a hand piece 110 and cannulaor probe shaft 102 which is shown after it is inserted in the nasalcavity 160 of a subject's nose 150. Although device 100 will bedescribed in further detail below, it can be understood that device 100may be designed so that cannula or probe shaft 102 is long enough toreach a desired tissue location when hand piece 110 is placed outside ofnasal cavity 160 as shown. In some embodiments, the user may place thetip of device 100 over a target area under endoscopic guidance. Byputting lateral pressure on the tip of the device 100, intimate contactwith the desired tissue location can be assured. The user may verify thecontact of the electrodes with the mucosal surface by using theendoscope (not shown in FIG. 1 ). In some embodiments, it may bedesirable to use device 100 without an endoscope, as will be describedin further detail below.

FIG. 2 shows a sagittal view of a human head with the device 100 and theendoscope 200 in the nasal cavity 160, in accordance with manyembodiments. As can be seen in FIG. 2 , a number of stimulatingelectrodes 104 may be disposed at the distal end of the device 100 andmay be placed over a target tissue area. Operation of a system withdevice 100 with stimulating electrodes 104 to stimulate and identify atarget nerve will be described with further reference to the figuresbelow. It can be seen from FIG. 2 that cannula 102 and electrodes 104are configured to reach a targeted location within the nasal cavity toeffect the desired stimulation and identification of target nerves. Forexample, cannula 102 and electrodes 104 may be configured to reach aregion of the nasal mucosa covering a medial pterygoid plate of sphenoidbone through a passage of a middle nasal meatus while handpiece 110 isoutside of the nasal cavity so as to target a posterior nasal nerve.

FIG. 3 shows a system 300, in accordance with many embodiments. As canbe seen in FIG. 3 , system 300 may include device 100 described above.Specifically device 100 may include device handle 110 which may beconnected to the cannula 102 and to an end effector 106. Cannula 102 mayhave a proximal end 114 and a distal end 116 at which end effector isdisposed. The end effector 106 may carry the nerve stimulatingelectrodes 104 on a surface thereof. As will be described in furtherdetail below, end effector 106 may also incorporate an ablation member.For example, end effector may incorporate a cryoablation member, an RFablation member, or any other suitable energy modality to ablate nerves.The device handle 110 may also be connected to an electrical source 304via a standard signal connector 108, which may interface with anysuitable cord 302. In this embodiment, the system 300 may be used byelectrically connecting the device handle 110 to the electrical source304 via any suitable electrical connection such as a cord 302 with aconnector that connects to a standard signal connector 108. Electricalsource 304 may provide a current through electrodes 104 to stimulatetissue, nerves, or other areas in contact with the electrodes 104.

As described above, since parasympathetic nerves, such as the posteriornasal nerve may respond to electrical stimulation with increased nasalsecretion or blood flow, the response to stimulation may be used toidentify a target nerve associated with secretory or vascular changes intissue innervated by the target nerve with system 300. Specifically, inorder to identify the target nerve, the end effector 106 may be placedover the region that the nerve(s) may be located, the electrical source304 may provide a current through electrodes 104 to stimulate theregion, and the response can be observed to determine whether the targetnerve has been located. Although this operation is explained below withreference to identifying nasal nerves that may be associated with one ormore symptoms of rhinitis, it will be understood that this onlyillustrative, and that embodiments may be directed to identifying othernerves associated with secretory or vascular changes in tissueinnervated by the target nerve.

In some embodiments, if the targeted nerve is a posterior nasal nerve(which may be associated with one or more symptoms of rhinitis, e.g.),then end effector 106 may be positioned in a general region where theposterior nasal nerve is expected. To avoid the need for visualization,this may be determined based on an anatomical landmark. For example, endeffector 106 may be placed adjacent to nasal mucosa covering a medialpterygoid plate of a sphenoid bone. Once positioned, the end effector106 may be pressed upon the target tissue area, and the electricalsource 304 can activate the electrical current through electrodes 104.In order to determine whether the nerve has been located, the user mayobserve the tissue which is innervated by the nerves that are beingstimulated. For example, the user may observe the turbinate whilestimulating the nasal tissue region. An increased flow of secretionsfrom the surface of mucosa or swelling of the turbinates may indicatethat the nerve has been located. If no increased secretion or swellingis identified, it may be determined that the nerve has not beenadequately located. Once the target nerve is located, the user canproceed to treat the nerve as desired to induce a change in thesecretory or vascular response of the tissue. For example, in the caseof the posterior nasal nerve as described above, the user may ablate thenerve so as to reduce the symptoms of rhinitis.

Although the target nerve may be identified by observing a response asdescribed above, it will be understood that in some embodiments, aresponse may be measured to identify the target nerve. It will beunderstood that the increased secretion or vascular response may bedetermined by measurement of various parameters. For example, sensors(not shown in FIGS. 1-3 ) may measure resistivity, conductivity, ortemperature in the target region to determine whether the desiredresponse associated with the target nerve has occurred, since secretionand/or vascular response may cause particular changes with suchparameters. As an example, since mucous typically contains electrolytesthat are capable of conducting electricity, increased nasal secretionmay be expected to result in decreased resistance in an associatedregion of the nose. Thus, the resistivity can be measured in the regionduring stimulation and a particular resistivity or change in resistivitymay indicate that the electrodes are located in the nearest vicinity ofthe target nerves. Similarly, the temperature in the region may increasein response to a particular vascular response that results fromstimulation of the targeted nerve, and temperature may be measured todetermine whether the electrodes are in the vicinity of the targetednerve.

In some embodiments, end effector 106 itself may be used as an ablationmember as described above. For example, end effector 106 may be used tocryogenically ablate a target nerve. A cryogen may be stored in handle110 at 112 and may be fluidly coupled via cannula 102 to the endeffector. Cryogen may be introduced to end effector from housing 112 viacontrol valve 118 to ablate regions surrounding end effector 106. Endeffector 106 may be configured to expand in response to introduction ofcryogen. If end effector 106 is not a cryogenic member, end effector maystill be configured to expand for reasons described herein. For example,end effector 106 may expand so as to position electrodes 104 in adesired location as will be described further below. In someembodiments, another device or treatment may be used to treat thelocated nerve. For example, the nerve may be ablated using a separateablation device, which may be a cryogenic ablation device, an RFablation device, or any other device using any other suitable energy toablate the nerve.

FIG. 4 shows connector 108 of device 100, in accordance with manyembodiments. As can be understood with reference to FIG. 4 , impulsesand return signals of the nerve stimulating elements may be routed fromelements inside the nasal cavity to the connector 108 at the bottom ofthe handle, where the stimulator 304 connects. In some embodiments,return signals may include signals from the electrodes or other sensorsdisposed on cannula 102 for measuring the response to stimulation asdescribed above.

FIG. 5 shows distal end 116 of device 100, which, as described above mayinclude nerve stimulating elements and ablation members, in accordancewith many embodiments. It will be understood that the nerve stimulatingelements can be in various arrangements depending on the desiredapplication and can be affixed to the distal end 116 of the device invarious ways. For example, stimulating elements may be embedded elementsthat can be applied to the exterior surface of the probe at the distalend 116 via metallic ink or thin metallic film. A number of arrangementsof stimulating elements that may be used with device 100 are describedbelow with reference to FIGS. 6-10 .

FIG. 6 shows an end effector 606 with electrodes 604A and 604B inaccordance with many embodiments. As can be seen in FIG. 6 , endeffector 606 may have a center electrode 604B disposed centrally on endeffector 606 and an outer electrode 604A that is disposed along theperimeter of end effector 606 so as to surround center electrode 604B.In operation, an electrical signal may be passed (from electrical source304 for example) to the center electrode 604B. The signal may then passthrough the tissue in contact with center electrode 604B and then to theouter electrode 604A. In this fashion, any nerves which may fall in thearea between the circular outer electrode 604A and the center electrode604B will receive the current and be stimulated. It will be understoodthat the distance between outer electrode 604A and center electrode 604Bmay dictate the depth of stimulation. Thus, the distance may be selectedso as to approach the targeted nerve. For example, the distance betweenelectrodes 604A and 604B may be a predetermined distance so as toachieve a depth of stimulation of 1 to 5 mm. In some embodiments, thedistance may be selected so as to achieve a depth of stimulation of 1 to3 mm. To achieve such a depth, it may be desirable to provide aseparation distance of about 1 mm to 10 mm.

FIG. 7 shows an alternate end effector 706 in accordance with manyembodiments. As can be seen in FIG. 7 , end effector 706 may includefour electrodes 704A-D as opposed to two electrodes. It will beunderstood that all four electrodes 704A-D may be coupled to electricalsource 304 so that current may be directed through any or all of theelectrodes 704A-D. The current will pass through the tissue betweenwhichever electrodes are activated and stimulate any intervening nervesas described above. This arrangement may allow a user to selectivelystimulate certain areas in contact with end effector 706 to moreprecisely stimulate and identify/locate a target nerve. For example,depending on which electrodes are used and the observed or measuredresponse to stimulation therein, a location in any one of four quadrantson the end effector may be determined, which may provide a more definedlocation of the nerve than using one or two electrodes. It will beunderstood that although multiple electrodes are used in a so-calledbipolar arrangements, in some embodiments, a single electrode may beused to stimulate and identify a nerve.

FIG. 8 shows a system 800 with a reusable stimulator tip 818 inaccordance with many embodiments. Reusable stimulator tip 818 may bereleasably coupled from the cannula 802 of probe 810 which may bedesirable, for example, to clean the stimulator between human uses.Specifically as seen in FIG. 8 , reusable stimulator tip 818 may beclicked onto the distal end 816 of the cannula 802 when in use, and maybe pulled off when not in use. When connected to cannula 802, reusablestimulator tip may extend past the energy probe 806 (which may be, e.g.a cryogenic ablation member or any other type of ablation member asdescribed above with respect to end effector 106) on the side that willnot be in contact with the lateral wall of the nasal cavity. Electrodeson reusable stimulator tip may be disposed at the distal tip 820 whichmay extend just distally of the energy probe 806, as will be describedbelow with respect to FIGS. 9A-9C. It can be seen that reusablestimulator tip 818, once clicked onto the cannula 802 may connect to thestimulator 304 via a low profile cable 302 that runs externally butadjacent to the cannula 302 of the device handle 810. The electrodes 804(not shown in FIG. 8 ) of the reusable stimulator tip 818 may bepositioned on the distal end facing perpendicular to the plane of theend effector 806, as will be described with reference to FIGS. 9A-9C.

FIGS. 9A-9C show views of reusable stimulator tip 818 and end effector806 in accordance with many embodiments. FIG. 9A shows a top view of theassembly 818 when coupled to cannula 802 and end effector 806, and FIG.9B shows the bottom view of the assembly 818 when coupled to cannula 802and end effector 806. FIG. 9C shows the side profile of reusablestimulator tip 818 affixed to cannula 802 and end effector. As can beseen in FIGS. 9A-9C, reusable stimulator tip 818 only extends along oneside of end effector 806 so as not to interfere with a side of endeffector 806 during operation. As can be particularly seen in FIG. 9C,reusable stimulator tip 818 hugs a bottom surface of end effector 806 soas not to increase the profile of the probe when inserted into thetarget region. The portion extending along the bottom of end effector806 may be a lever spring arm 822.

Lever spring arm 822 may end at a distal tip 820 which is disposeddistally of the end effector 806. In some embodiments, electrodes 804Aand 804B may be disposed at the distal tip 820 of lever spring arm 822,as shown in FIGS. 9A and 9B. Although shown as two spaced apartelectrodes, any suitable arrangement of electrodes may be used at distaltip 820 as described above. For example, distal tip 820 may be designedto extend along a larger portion of the perimeter of end effector 806and a number of electrodes may be provided thereon. Lever spring arm 822may be spring biased to keep distal tip 820 and electrodes 804A and 804Bin contact with the desired region of tissue when in use.

FIG. 10 shows reusable stimulator tip 818 unattached to device 810 inaccordance with many embodiments. As can be seen in FIG. 10 , theelectrodes 804A and 804B of the stimulator tip 818 may be positioned onthe distal end 820 facing perpendicular to the plane of the stimulatortip 818. As described above, the stimulator tip 818 is designed toensure the electrodes 804A and 804B stay in positive contact with themucosal lining throughout use in the nasal cavity once clicked onto thecannula 802 by using a lever spring arm 822 also shown illustrated inFIG. 10 . In some embodiments, the stimulator tip 818 can be made out ofan injection moldable semi-rigid plastic (i.e. polyimide) or a temperedstainless steel. For example, the semi rigid plastic or stainless steelalong with the geometry of the arm 822 may create a positive lateralforce to ensure the electrodes 804A and 804B contact the relevant tissue(e.g. the mucosa) while positioning the probe for stimulation. Asdescribed above, the reusable stimulator tip 818 is designed to hug theenergy probe 806 to minimize the added profile to ensure distal portionof the instrument can navigate around the structures in the nasalpassageway.

As can be seen in FIG. 10 , reusable stimulator tip 818 may include aconnector 824 that snaps onto cannula 802. Although shown as a snap-onconnector that may wrap around cannula 802, it will be understood thatconnector 824 may include any suitable connector for connecting tocannula 802 as described. In order to electrically couple stimulatingelectrodes 804A and 804B to an electrical source, the proximal end ofreusable stimulator tip 818 may include a low-profile cord 826electrically coupled to the electrodes 804A, 804B and configured to beelectrically coupled to the electrical source 304. Cord 826 may beconnected to or a part of cord 302 described above with respect to FIG.8 , and may run externally along (but adjacent to) cannula 802.

FIG. 11 shows a coronal view of the relative location of an end effector1104 with respect to anatomical landmarks in the nasal cavity, inaccordance with many embodiments. As can be seen, in some embodiments,it may be desirable to target a location between a middle turbinate 1108and lateral wall 1112 by positioning end effector 1104 therein. Thislocation may allow targeting of a nasal nerve such as the posteriornasal nerve, which is associated with symptoms of rhinitis, as describedabove. It can be seen that in some cases the target location may requirea low profile device as described above.

FIG. 12A shows a diagram tracing the current flow through the tissuethat stimulates the nerve, in accordance with many embodiments. As canbe seen in FIG. 12A, the distance between electrodes 1204, which may bedisposed on end effector in the deflated state 1206A may be selected toachieve a desired depth of stimulation so that current 1208 reaches atargeted nerve 1210. In some embodiments, end effector may be inflatedinto its inflated position 1206B as described previously. FIG. 12B showsthe diagram of FIG. 12A with end effector in its inflated position1206B, in accordance with many embodiments. It can be seen that puttingend effector in its inflated position 1206B may allow electrodes 1204 tobe more closely in contact with the targeted nerve 1210. This may allowfor a more pronounced effect when stimulating and/or ablating thetargeted nerve 1210.

FIG. 13 shows the distal end of a probe 1301 with conductivity sensors1304 in accordance with many embodiments. As can be seen in FIG. 13 ,the distal end 1302 of probe 1301 may be placed in contact with adesired region expected to be innervated by the target nerves. Forexample, the distal end 1302 may be positioned to contact a regionexpected to be innervated by a posterior nasal nerve. In order toidentify and locate the targeted nerve, electrical current may beprovided to stimulating electrodes 1303. Rather than rely on an observedresponse to the stimulation, in some embodiments, probe 1301 may includeconductivity detectors 1304. Detectors 1304 may be located proximally ofthe stimulating electrodes 1303 so as to detect conductivity in adesired region proximal of the nerve. For example, stimulation of anerve may result in secretion at a proximal location of the stimulation,so it may be desirable to locate the conductivity detectors accordingly.As can be seen in FIG. 13 , conductivity sensors may be configured todetect conductivity between two points, which conductivity may beindicative of increased secretion as described above. Although not shownhere, conductivity sensors 1304 may be coupled to a processor andassociated computing device that may be able to monitor the conductivityin response to stimulation and determine when the stimulating electrodesare suitably close to a target nerve. The computing device may beconfigured to alert the user when a target nerve is identified using anysuitable alert including a visual alert, an audio alert, or a hapticalert. Although shown here as conductivity sensors, sensors 1304 may beany suitable sensor to measure any of the parameters described hereinthat may indicate increased secretion or a desired vascular response.For example, temperature sensors or other sensors may be used in placeof or in addition to conductivity or resistivity sensors. Any of thesensors described herein to measure the response to stimulation may belocated anywhere on probe 1301. For example, sensors may be embeddedonto electrodes 1303 or on other portions of the end effector 1306.

In some embodiments, it may be advantageous to use separate devices fornerve identification and ablation. For example, if multiple locations ofablation are required, it may be beneficial to first identify and mapall of the nerve locations and then perform ablation. This may bebeneficial because ablation after an initial target nerve is located mayaffect sensing other target nerves in the vicinity. This may also bebeneficial because the user would be able to use a very small tipdiameter, between 0.5 mm and 5 mm to map the locations of the nerves asdescribed before which may provide improved precision and/or resolution.Accordingly, image guided navigation systems and methods for identifyingtarget nerves are described according to many embodiments.

FIG. 14 shows a simplified illustration of an image guided navigationsystem for ablation in accordance with many embodiments. In someembodiments, the navigation system would place a mark on each targetlocation during the nerve detection step so that the location can beeasily and precisely identified subsequently with an ablation device.The system may store coordinates of each identified target location anddisplay them on an image for subsequent ablation. As seen in FIG. 14 ,once the locations have been determined, a display 1402 may show theuser the identified target locations 1404 and the current location 1406of the ablation probe attached to device 1410 in real time. This wouldallow the user to use one device to identify multiple target locations1404 without affecting other areas in the same vicinity by ablationthereof. Once stored, the user may use the image guidance with thecurrent location of the ablation probe 1406 shown in real time and theidentified target nerve locations 1404 to easily and precisely ablatethe target locations. In some embodiments, the ablation tip may not haveelectrodes on it. It can be seen that by tracking the ablation devicewith the guidance system, the proper target locations can be approached,contacted and ablated.

FIG. 15 is a flowchart illustrating a method 1500 of nerveidentification and/or ablation, in accordance with many embodiments. Itwill be understood by those skilled in the art that the order of thesteps may be switched, some of the steps may be combined, and/or some ofthe steps may be optional. The flowchart of FIG. 15 is one example ofthe method and is not intended to be limiting. Thus, it will beunderstood by those skilled in the art that various other operation(s)disclosed in this application may be used instead of those shown in FIG.15 . Method 1500 may be performed by any or all of the systems andcomponents described above. For example, method 1500 may be performed byany of device 100, systems 300, 800, 1300, 1400, associated componentsthereof and/or any suitable combination thereof. The steps of method1500 will now be described with reference to FIG. 15 .

At step 1501, electrodes of a stimulator probe may be positioned at adesired location. For example, a distal end of a probe device such asdevice 100 may be inserted into a nasal cavity and positioned so thatelectrodes 104 are disposed adjacent to a region where a target nerve isexpected to be located. The positioning may be done based on ananatomical landmark. In some embodiments, the positioning may furtherinclude expanding an end effector such as end effector 106 to place theelectrodes in closer contact to the desired region.

Once the electrodes are positioned, at step 1502, a stimulus may beapplied to the electrodes. In some embodiments, a pulsing stimulus maybe applied to the electrodes by electrical source such as electricalsource 304 described above with respect to systems 300 and/or 800. Anyof the voltage, frequency, pulse rate, and current may be selected toobtain a particular response from the stimulation. For example, FIG. 16shows experimental data illustrating the relationship between pulse rateand stimulation frequency and secretion. Accordingly, stimulation may becontrolled using any of the prescribed parameters shown in FIG. 17 ,which shows some desirable electrical stimulation parameters inaccordance with some embodiments. In some embodiments, the desiredresponse may require delivering electric pulses through the electrodesat a frequency in a range from about 0.5 to about 12 impulses persecond.

At step 1503, it is determined whether the desired response is obtained.As described above, this may be done by observation of the target tissueregion and surrounding tissue for increased secretion and/or increasedblood flow or other vascular response. For example, a desired result maybe an increased secretion that indicates the electrodes are positionednear the targeted nerve. In some embodiments, the desired response maybe determined based on a measured parameter including conductivity,resistivity, temperature, or other relevant parameter that may indicateincreased secretion or vascular response. The desired response may bedetermined by a processor coupled to sensors disposed on the device asdescribed above with respect to FIG. 13 .

If it is determined that the desired response is not obtained, at step1504, the electrode may be repositioned for further stimulation. Forexample, if no secretion or vascular response are observed in responseto the stimulation, it may be determined that the electrodes are notnear the targeted nerve, and they may be repositioned. As anotherexample, if a threshold measurement is not sensed by relevant sensorsdescribed above, it may be determined that the electrodes are notadequately near the targeted nerve and they may be repositioned. Oncerepositioned, stimulus may be applied again as described with respect tostep 1502 above.

If the desired response is obtained at step 1503, and an integratedablation device is being used as determined at step 1505, then thetargeted nerve may be ablated at step 1506. For example, if a devicesuch as device 100 with both stimulating electrodes 104 and an ablationmember 106 is being used, once the desired response is obtained at step1503, the ablation member 106 may be used immediately to ablate thetargeted nerve. In some embodiments, depending on the relative locationof the electrodes and the ablation device, an optional step of adjustingthe positioning of the ablation member may be needed after determiningthat the desired response is obtained. For example, if the electrodesare disposed distally of the ablation member (such as in system 800),the probe may be inserted further to align the ablation member with theidentified target nerve for precise ablation.

If the desired response is obtained at step 1503, and an integratedablation device is not being used as determined at step 1505, then thelocation may be marked at step 1507. For example, the coordinates of theidentified target nerve may be stored as described above for use with animage guidance navigation system. Once the location is marked, it isdetermined whether additional target locations need to be identified atstep 1508. If additional locations need to be identified, then theelectrode may be repositioned as desired at step 1509. Oncerepositioned, stimulus may be applied again as described with respect tostep 1502 above and the process may repeat as necessary until alllocations are identified and/or marked.

If it is determined at step 1508 that no additional locations need to beidentified, then the separate ablation member may be positioned forablation at step 1510. Once positioned at a marked location, theablation member may be used to ablate the target nerve at step 1506. Ifmultiple target nerves or locations of a target nerve were marked,ablation member may be repositioned to each of the marked locations forablation. It will be understood that image guided navigation may beemployed as described above with respect to FIG. 14 in order to mark andrecall the locations of target nerves.

Once ablation is performed at step 1510, the ablation may be confirmedat step 1511. For example, ablation may be confirmed by re-applyingstimulus using the electrodes as described above with respect to step1502, and observing or measuring the response thereto as described atstep 1503. If no response (e.g. no increased secretion or vascularresponse in the region), or a response below a desired threshold isobserved and/or measured, ablation may be complete and the process mayend (or proceed to other target locations as described above). If aresponse such as increased secretion is observed and/or measured inresponse to the re-applied stimulus, the desired ablation may not becomplete, and ablation may be repeated as described above with respectto step 1506 until ablation is confirmed. In some embodiments, it may bedesirable to provide a waiting period after ablation at step 1506 andbefore re-applying stimulus to confirm ablation at step 1511. Thewaiting period may allow the region to recover so that an accurateevaluation of whether satisfactory ablation has been achieved can beobtained at step 1511.

Other variations are within the spirit of the present invention. Thus,while the invention is susceptible to various modifications andalternative constructions, certain illustrated embodiments thereof areshown in the drawings and have been described above in detail. It shouldbe understood, however, that there is no intention to limit theinvention to the specific form or forms disclosed, but on the contrary,the intention is to cover all modifications, alternative constructions,and equivalents falling within the spirit and scope of the invention, asdefined in the appended claims. For example, while symptoms of rhinitisand nasal nerves are described herein, it will be appreciated that anynerves which induce secretory or vascular changes in the tissueinnervated by such nerves may be targeted, stimulated, identified,and/or ablated as described herein.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted. The term “connected” is to beconstrued as partly or wholly contained within, attached to, or joinedtogether, even if there is something intervening. Recitation of rangesof values herein are merely intended to serve as a shorthand method ofreferring individually to each separate value falling within the range,unless otherwise indicated herein, and each separate value isincorporated into the specification as if it were individually recitedherein. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein, is intended merely to betterilluminate embodiments of the invention and does not pose a limitationon the scope of the invention unless otherwise claimed. No language inthe specification should be construed as indicating any non-claimedelement as essential to the practice of the invention.

Preferred embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention.Variations of those preferred embodiments may become apparent to thoseof ordinary skill in the art upon reading the foregoing description. Theinventors expect skilled artisans to employ such variations asappropriate, and the inventors intend for the invention to be practicedotherwise than as specifically described herein. Accordingly, thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

1. A system for ablating at least one nasal nerve associated with atleast one symptom of rhinitis, the system comprising: a probe shafthaving a proximal end and a distal end; an end effector permanentlycoupled to the distal end of the probe shaft; at least two electrodesdisposed at the distal end of the probe shaft, the at least twoelectrodes electrically coupled to an electrical source, wherein the atleast two electrodes are configured to electrically stimulate at leastone nasal nerve underlying a nasal surface in contact with the least twoelectrodes in response to an electrical current generated by theelectrical source, wherein the least two electrodes are configured todetect a parameter indicative of a physiologic response to theelectrical current; a processor operatively coupled to the electricalsource, wherein the processor is configured to: control the electricalcurrent generated by the electrical source, receive the parameterindicative of the physiologic response to the electrical current,wherein the physiologic response is at least one physiologic responseselected from a group consisting of: a change in nasal secretion and achange in arterial blood flow, and control, based on the parameter, theelectrical current generated by the electrical source to cause the leasttwo electrodes to ablate the at least one nasal nerve underlying thenasal surface to reduce the at least one symptom associated withrhinitis.
 2. The system of claim 1, wherein the processor is furtherconfigured to: measure a response to the electrical current using the atleast two electrodes; and provide an indication to reposition the probeand stimulating the at least two electrodes until a desired response ismeasured using the at least two electrodes.
 3. The system of claim 1,wherein the probe shaft is sized so that the distal end of the probeshaft can reach a nasal mucosa covering a medial pterygoid plate ofsphenoid bone through a passage of a middle nasal meatus from outside anasal cavity.
 4. The system of claim 1, wherein the processor isconfigured to control at least one feature selected from a groupconsisting of: a voltage, a frequency, and a pulse rate of theelectrical current.
 5. The system of claim 1, wherein the parameter isat least one parameter selected from a group consisting of: anelectrical resistance, a temperature, and a degree of tumescence of theat least one nasal nerve underlying the nasal surface.
 6. The system ofclaim 5, wherein the at least two electrodes are configured to detect achange in electrical resistance in an electrical signal passing throughthe at least two electrodes after stimulation of the at least one nasalnerve underlying the nasal surface, the change in resistance beingindicative of a change in nasal secretion after stimulation of the atleast one nasal nerve underlying the nasal surface.
 7. The system ofclaim 1, wherein the end effector comprises an expandable ablationmember.
 8. The system of claim 7, wherein the expandable ablation membercomprises an electrically non-conductive surface, and wherein the atleast two electrodes are disposed on the electrically non-conductivesurface of the expandable ablation member.
 9. The system of claim 7,wherein a first electrode of the at least two electrodes is disposed ata central location of the expandable ablation member, and a secondelectrode of the at least two electrodes is disposed along a perimeterof the expandable ablation member.
 10. The system of claim 7, whereinthe at least two electrodes comprises four electrodes arrangedrectangularly on the expandable ablation member such that the fourelectrodes are configured to stimulate four quadrants of the expandableablation member.
 11. The system of claim 7, wherein the expandableablation member is configured to inflate so as to position the at leasttwo electrodes adjacent to the nasal surface.
 12. The system of claim 7,wherein the expandable ablation member comprises an expandablecryoablation member configured to cryogenically ablate the at least onenasal nerve to reduce at least one symptom associated with rhinitis. 13.The system of claim 1, wherein the at least two electrodes are disposedon a distal tip that is releasably coupled to the probe shaft.
 14. Thesystem of claim 13, wherein the distal tip includes a connector that iscoupled to a connection portion of the probe shaft that is proximal tothe end effector.
 15. The system of claim 14, wherein the distal tipextends from the connection portion to a distal end disposed distally ofthe end effector, and wherein the at least two electrodes are disposedat the distal end of the distal tip such that the at least twoelectrodes are distal to the end effector.
 16. The system of claim 1,wherein the processor is further configured to: control the electricalcurrent generated by the electrical source through the at least twoelectrodes after ablating the at least one nasal nerve to confirm thatthe at least one nasal nerve has been ablated.
 17. The system of claim1, further comprising: at least one sensor, wherein the sensor isconfigured to detect the parameter indicative of a physiologic responseto the electrical current, and wherein the at least one sensor isdisposed on the probe shaft.
 18. The system of claim 1, whereincontrolling the electrical current generated by the electrical sourcecomprises delivering electric pulses through the at least two electrodesat a frequency between 0.5 impulses per second to 12 impulses persecond.
 19. The system of claim 1, wherein the at least two electrodesare spaced apart in a range from 1 mm to 10 mm.
 20. The system of claim1, wherein the at least two electrodes are configured to stimulate 1 mmto 3 mm under the nasal surface in contact with the at least twoelectrodes.